TOTAL SYNTHESIS AND ABSOLUTE-CONFIGURATION OF PSEUDOSEMIGLABRIN, A PLATELET-AGGREGATION ANTAGONIST, AND ITS DIASTEREOMER SEMIGLABRIN

A general approach to the synthesis of the flavone-furo[2,3-b]furan ri ng system present in numerous biologically-active secondary metabolite s of Tephrosia sp. has been developed and applied in one racemic synth esis and two asymmetric syntheses of four members of the family. It us es 2-diazo-1,3-cyclohexanedione as the keystone of the ring system, un iting it with a dihydrofuran through a rhodium-mediated dipolar cycloa ddition. The enolate of this tricyclic intermediate is then utilized t o elaborate a salicylate that is subjected to a concise annulation pro tocol with benzaldehyde to produce the tetracycle. Stereochemical cont rol is accomplished by the use of three strategies. Reduction of a ket one from the more accessible face of a folded bicyclooctane ring syste m produces the endo stereochemistry. Steric hindrance by a bulky allyl ic siloxy group directs the cycloaddition to the opposite face of the prochiral alkene to generate the exo stereochemistry. Finally, a novel hydroxyl-directed cycloaddition simultaneously produces the endo ster eochemistry and accesses the opposite enantiomeric series.